Granulocyte colony-stimulating factor treatment ameliorates lupus nephritis through the expansion of regulatory T cells
Open Access
- 15 November 2016
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Nephrology
- Vol. 17 (1), 1-12
- https://doi.org/10.1186/s12882-016-0380-x
Abstract
Granulocyte colony-stimulating factor (G-CSF) can induce regulatory T cells (Tregs) as well as myeloid-derived suppressor cells (MDSCs). Despite the immune modulatory effects of G-CSF, results of G-CSF treatment in systemic lupus erythematosus are still controversial. We therefore investigated whether G-CSF can ameliorate lupus nephritis and studied the underlying mechanisms. NZB/W F1 female mice were treated with G-CSF or phosphate-buffered saline for 5 consecutive days every week from 24 weeks of age, and were analyzed at 36 weeks of age. G-CSF treatment decreased proteinuria and serum anti-dsDNA, increased serum complement component 3 (C3), and attenuated renal tissue injury including deposition of IgG and C3. G-CSF treatment also decreased serum levels of BUN and creatinine, and ultimately decreased mortality of NZB/W F1 mice. G-CSF treatment induced expansion of CD4+CD25+Foxp3+ Tregs, with decreased renal infiltration of T cells, B cells, inflammatory granulocytes and monocytes in both kidneys and spleen. G-CSF treatment also decreased expression levels of MCP-1, IL-6, IL-2, and IL-10 in renal tissues as well as serum levels of MCP-1, IL-6, TNF-α, IL-10, and IL-17. When Tregs were depleted by PC61 treatment, G-CSF-mediated protective effects on lupus nephritis were abrogated. G-CSF treatment ameliorated lupus nephritis through the preferential expansion of CD4+CD25+Foxp3+ Tregs. Therefore, G-CSF has a therapeutic potential for lupus nephritis.Keywords
Funding Information
- Ministry of Health and Welfare, Republic of Korea (A120641)
This publication has 34 references indexed in Scilit:
- The granulocyte colony stimulating factor pathway regulates autoantibody production in a murine induced model of systemic lupus erythematosusArthritis Research & Therapy, 2013
- CD4+Foxp3+ regulatory T cells prolong drug-induced disease remission in (NZBxNZW) F1 lupus miceArthritis Research & Therapy, 2013
- Attenuation of nephritis in lupus-prone mice by thalidomideRheumatology, 2012
- MDSC in autoimmunityInternational Immunopharmacology, 2011
- In Vivo Induction of Myeloid Suppressor Cells and CD4+Foxp3+T Regulatory Cells Prolongs Skin Allograft Survival in MiceCell Transplantation, 2011
- Targeting transcription factor Stat4 uncovers a role for interleukin-18 in the pathogenesis of severe lupus nephritis in miceKidney International, 2011
- Involvement of CD11b+ GR-1low cells in autoimmune disorder in MRL-Fas lpr mouseClinical and Experimental Nephrology, 2010
- Granulocyte Colony-Stimulating Factor for the Induction of T-Cell ToleranceTransplantation, 2007
- Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythematosusProceedings of the National Academy of Sciences of the United States of America, 2006
- Prostaglandin e1 treatment of NZB/NZW F1 hybrid MICEArthritis & Rheumatism, 1977